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Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma.

ABSTRACT:

Abstract

Locally advanced nasopharyngeal carcinoma (LA-NPC) is more prevalent in some geographic regions, including Saudi Arabia. Typically, Tumor-Node-Metastasis (TNM) staging is used in NPC. However, it is inadequate to assess the prognosis of LA-NPC.Therefore, we analyzed and compared several previously reported prognostic factors in LA-NPC patients, retrospectively, including CD3+tumor-infiltrating lymphocytes (TIL) and peripheral blood hemoglobin, EBV DNA copy number, ratios of albumin-to-alkaline phosphatase ratio (AAPR), neutrophils, or platelets-to-lymphocytes (NLR, PLR). The studied cohort was 83 LA-NPC patients previously recruited for a randomized phase II trial with a different aim.Univariate cox regression analysis showed no significant correlation between any of the tested variables with disease-free survival (DFS) or overall survival (OS) with the exception of low CD3+ TIL infiltration, which correlated significantly with DFS (HR = 6.7, P = <.001) and OS (HR = 9.1, P = .043). Similarly, in a validated multivariate cox regression analysis, only low CD3+ TIL correlated significantly with DFS (HR = 7.0, P < .001 for TIL) and OS (HR = 9.4, P = .040).Among tested parameters, CD3+ TIL was the only independent prognostic marker for DFS and OS in LA-NPC patients treated with CCRT. This study supports the use of CD3+TIL, over other factors, as an independent prognostic factor in LA-NPC.

SUBMITTER: Al-Rajhi N

PROVIDER: S-EPMC8601301 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma.

Al-Rajhi Nasser N Mohammed Shamayel F SF Khoja Hatim A HA Al-Dehaim Mohammad M Ghebeh Hazem H

Medicine 20211101 46

<h4>Abstract</h4>Locally advanced nasopharyngeal carcinoma (LA-NPC) is more prevalent in some geographic regions, including Saudi Arabia. Typically, Tumor-Node-Metastasis (TNM) staging is used in NPC. However, it is inadequate to assess the prognosis of LA-NPC.Therefore, we analyzed and compared several previously reported prognostic factors in LA-NPC patients, retrospectively, including CD3+tumor-infiltrating lymphocytes (TIL) and peripheral blood hemoglobin, EBV DNA copy number, ratios of albu ...[more]

PMID: 34797353

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Project description:BackgroundLocally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively rare disease in the west but more common in East Asia and areas of the Middle East like Saudi Arabia. Despite the advances in radiation therapy techniques, some patients relapse after treatment. In the coming era of cancer immunotherapy, prognostic factors for LA-NPC need to be further defined using immune-relevant markers. Several markers are available; however, the most robust and accessible/affordable marker is not well-defined.MethodsRetrospectively, tumor-infiltrating lymphocytes (TIL), their subsets as well as tumoral PD-L1 expression were analyzed in tumor tissues from 63 LA-NPC patients treated with platinum-based concurrent chemo-radiotherapy (CCRT) in addition to 20 cases with metastatic (MET) disease. Immunostaining was done using a validated and fully automated system. Scoring was done by two independent pathologists and results were compared.ResultsThere was no statistical difference between LA-NPC and MET disease in terms of CD3+, CD8+ TIL infiltration, or tumoral PD-L1 expression. In LA-NPC, low CD3+ TIL infiltration highly correlated with shorter disease-free survival (DFS, HR = 8.5, p = < 0.001) and overall survival (OS, HR = 13, p = 0.015) with substantial agreement between scoring pathologists. A similar correlation was found between low CD8+ TIL and survival. Correlation of total TIL was significant with DFS (HR = 4.0, p = 0.008), borderline with OS and the correlation was dependent on the scoring pathologist. Having histological WHO type I&II correlated significantly with shorter DFS (HR 4.03, p = 0.008) and low CD3+ TIL (p = 0.009). Subgroup analysis of LA-NPC that included undifferentiated type (WHO type III) cases only (n = 58), showed a strong correlation between low CD3+ TIL and shorter DFS (HR = 7.2, p = < 0.001) and OS (HR = 17.3, p = 0.008). PD-L1 was expressed in 72% of type III LA-NPC cases while lacking PD-L1 expression correlated with shorter OS (HR = 6.1, p = 0.031). Patients with a combination of low CD3+ TIL and lack of PD-L1 expression had the worst OS (p < 0.001).ConclusionsCD3+ TIL is promising as a robust and independent prognostic marker for DFS and OS of LA-NPC patients treated with platinum-based CCRT. We would suggest the use of CD3 + TIL as a stratifying factor for LA-NPC, which warrants further validation in prospective trials.

Project description:PurposeConcurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta-analysis investigates the value of adding ICT to CCRT in LA-NPC.Materials and methodsTwo reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment-naive adult patients with histologically proven nonmetastatic LA-NPC.ResultsEight RCTs with in total 2,384 randomized patients, of whom 69% had N2-N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%-100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) -0.001-0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, -0.243; 95% CI, -0.403 to -0.083; p = .003). Grade 3-4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511-0.905; p = .001) and progression-free survival (HR, 0.657; 95% CI, 0.568-0.760; p < .001).ConclusionAlthough ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA-NPC, but further study on optimal patient selection for this treatment is warranted.Implications for practiceLocally advanced nasopharyngeal carcinoma (LA-NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta-analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA-NPC is associated with a significant clinical improvement in both overall survival and progression-free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA-NPC.

Project description:PurposeTo explore the prognostic impact of combined tumor-infiltrating lymphocytes (TILs) and pretreatment peripheral lymphocyte percentage (LYM%) among patients with locally advanced nasopharyngeal carcinoma (LA-NPC).Patients and methodsTILs and pretreatment LYM% were retrospectively assessed in 253 LA-NPC patients who underwent chemoradiation therapy between January 2012 and December 2017. According to TILs and LYM% status, the patients were divided into three groups: high-risk group (HRG) (TILs-LYM% score = 0), middle-risk group (MRG) (TILs-LYM% score = 1), and low-risk group (LRG) (TILs-LYM% score = 2). The relationship between TILs level and LYM%, and also the associations of TILs-LYM% status with clinicopathological factors and survival, were evaluated.ResultsAs a continuous variable, LYM% was significantly higher in TILs-high group. High TILs or high LYM% alone was significantly related to better 3-year disease-free survival (DFS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRRFS), respectively. Kaplan-Meier analysis and log-rank tests also revealed significant decreases in DFS, OS, DMFS, and LRRFS among LA-NPC patients with TILs-LYM% score of 0, 1, and 2 (all P <0.05). Further multivariate analyses showed that TILs-LYM% score was an independent factor affecting survival of the patients, and HRG (TILs-LYM% score = 0) had increased hazard ratios (HRs) for disease (HR = 6.89, P <0.001), death (HR = 8.08, P = 0.008), distant metastasis (HR = 7.66, P = 0.001), and local relapse (HR = 5.18, P = 0.013) compared with LRG (TILs-LYM% score = 2). In receiver operating characteristics (ROC) analyses, TILs-LYM% score had a higher area under the ROC curve (AUC) for the prediction of DFS than did TILs or LYM% alone.ConclusionsA positive correlation was found between TILs level and pretreatment blood lymphocyte percentage. Moreover, TILs-LYM% score can be considered as a novel independent prognostic indicator of survival outcome among patients with LA-NPC.

Project description:ImportanceEsophageal squamous cell carcinoma (ESCC) is a deadly disease with frequent recurrence. There are unmet needs for prognostic biomarkers for dynamically monitoring disease progression and detecting minimal residual disease.ObjectiveTo examine whether circulating tumor DNA is clinically useful as a prognostic biomarker for ESCC recurrence and patient survival.Design, setting, and participantsThis single-center, population-based cohort study consecutively enrolled 147 patients receiving curative (n = 74) or palliative (n = 73) treatment at the surgery and clinical oncology departments of Queen Mary Hospital in Hong Kong from August 1, 2016, to September 31, 2021. Patients were followed up for 2 years. Plasma samples were collected at different longitudinal time points for a prospective circulating tumor DNA (ctDNA) next-generation sequencing profiling study of 77 actionable genes.InterventionPatients were treated with up-front surgery, neoadjuvant chemoradiotherapy plus surgery with or without adjuvant therapy, or palliative chemotherapy (CT).Main outcomes and measuresDetection of circulating tumor DNA (ctDNA), progression-free survival (PFS), and overall survival (OS).ResultsA total of 478 serial plasma samples from 147 patients with locoregional or metastatic ESCC were prospectively analyzed. Among the 74 patients in the curative group (median [range] age, 66 [46-85] years; 56 [76.0%] male), 44 (59.5%) relapsed and 36 (48.6%) died. For patients receiving curative surgical treatment, a high ctDNA level (hazard ratio [HR], 7.84; 95% CI, 1.87-32.97; P = .005) and ctDNA alterations (HR, 5.71; 95% CI, 1.81-17.97; P = .003) at 6 months postoperation were independently associated with poor OS. Among patients receiving neoadjuvant chemoradiotherapy, postneoadjuvant ctDNA alterations were associated with poor PFS (HR, 3.16; 95% CI, 1.17-8.52; P = .02). In the 73 patients in the palliative group (median [range] age, 63 [45-82] years; 63 [86.0%] male), 71 (97.3%) had disease relapse and 68 (93.2%) died. Detectable pre-CT NFE2L2 alterations were independently associated with PFS (HR, 2.99; 95% CI, 1.35-6.61; P = .007) and OS (HR, 28.39; 95% CI, 7.26-111.03; P = 1.52 × 10-6), whereas high ctDNA levels (HR, 2.41; 95% CI, 1.18-4.95; P = .02) and alterations in pre-cycle III ctDNA (HR, 1.99; 95% CI, 1.03-3.85; P = .04) showed weaker associations with PFS. Alterations in pre-CT ctDNA were independently associated with OS (HR, 4.46; 95% CI, 1.86-10.69; P = 7.97 × 10-4).Conclusions and relevanceThe findings of this cohort study indicate that prognostic models incorporating ctDNA features are useful in ESCC. Both ctDNA level and NFE2L2 alterations pre-CT and before cycle III were found to be important prognostic factors in palliative groups, and ctDNA alterations after treatment and at 6 months after surgery may define high-risk groups for recurrence in the curative group. High-risk patients can benefit by a timely switch to the next therapeutic options.

Project description:Background: Recurrence remains one of the key reasons of relapse after the radical radiation for locally advanced nasopharyngeal carcinoma (NPC). Here, the multiple molecular and clinical variables integrated decision tree algorithms were designed to predict individual recurrence patterns (with VS without recurrence) for locally advanced NPC. Methods: A total of 136 locally advanced NPC patients retrieved from a randomized controlled phase III trial, were included. For each patient, the expression levels of 33 clinicopathological biomarkers in tumor specimen, 3 Epstein-Barr virus related serological antibody titer and 5 clinicopathological variables, were detected and collected to construct the decision tree algorithm. The expression level of 33 clinicopathological biomarkers in tumor specimen was evaluated by immunohistochemistry staining. Results: Three algorithm classifiers, augmented by the adaptive boosting algorithm for variable selection and classification, were designed to predict individual recurrence pattern. The classifiers were trained in the training subset and further tested using a 10-fold cross-validation scheme in the validation subset. In total, 13 molecules expression level in tumor specimen, including AKT1, Aurora-A, Bax, Bcl-2, N-Cadherin, CENP-H, HIF-1α, LMP-1, C-Met, MMP-2, MMP-9, Pontin and Stathmin, and N stage were selected to construct three 10-fold cross-validation decision tree classifiers. These classifiers showed high predictive sensitivity (87.2-93.3%), specificity (69.0-100.0%), and overall accuracy (84.5-95.2%) to predict recurrence pattern individually. Multivariate analyses confirmed the decision tree classifier was an independent prognostic factor to predict individual recurrence (algorithm 1: hazard ration (HR) 0.07, 95% confidence interval (CI) 0.03-0.16, P < 0.01; algorithm 2: HR 0.13, 95% CI 0.04-0.44, P < 0.01; algorithm 3: HR 0.13, 95% CI 0.03-0.68, P = 0.02). Conclusion: Multiple molecular and clinicopathological variables integrated decision tree algorithms may individually predict the recurrence pattern for locally advanced NPC. This decision tree algorism provides a potential tool to select patients with high recurrence risk for intensive follow-up, and to diagnose recurrence at an earlier stage for salvage treatment in the NPC endemic region.

Dataset Information

Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma.

Abstract

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Prognostic markers compared to CD3+TIL in locally advanced nasopharyngeal carcinoma.

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